S0429: Docetaxel, Cetuximab, and Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer

This study has been terminated.
(Study closed early due to poor accrual.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00288054
First received: February 6, 2006
Last updated: January 2, 2013
Last verified: January 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving docetaxel and cetuximab together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of docetaxel when given together with cetuximab and radiation therapy in treating patients with stage III non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Biological: cetuximab
Drug: docetaxel
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot (Phase I) Study of Weekly Docetaxel and Cetuximab Chemoradiation for Poor Risk Stage III Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Treatment-related Esophagitis or Pneumonitis [ Time Frame: Weekly for the first 8 weeks, then every 4 weeks thereafter for up to 4 months after complettion of radiotherapy. ] [ Designated as safety issue: Yes ]
    The primary endpoint will be the rate of Grade 3 or greater esophagitis and/or pneumonitis within 4 months after discontinuation of radiation therapy.


Secondary Outcome Measures:
  • Toxicity [ Time Frame: Weekly for the first 8 weeks, then every 4 weeks while subject on protocol treatment. ] [ Designated as safety issue: Yes ]
    Only adverse events that are possibly, probably or definitely related to study drug are reported.

  • Overall Survival [ Time Frame: weekly while patient is on protocol treatment, then monthly thereafter. ] [ Designated as safety issue: No ]
    The duration form the date of enrollment until the date of death due to any cause. Patients last known to be alive are censored at the date of last contact.

  • Progression-free Survival. [ Time Frame: At week 10, week 22, and then every 3 months until progression for up to 3 years after enrollment. ] [ Designated as safety issue: No ]
    Duration from the date of enrollment until the date of progression (as defined by RECIST: >= 20% increase over baseline in the sum of longest diameters, or appearance of new lesions, or non-measurable disease that is clearly worsening in the opinion of the treating investigator, or symptomatic deterioration) or death due to any cause. Patients last known to be alive and free of disease progression are censored at the date of last contact.

  • Response Rate [ Time Frame: Week 10 and week 22 ] [ Designated as safety issue: No ]
    Confirmed and unconfirmed complete and partial responses in the subset of patients with measurable disease (as defined per RECIST). A confirmed complete response (CR) is defined as disappearance of all disease, confirmed by a second determination of CR at least 4 weeks later. A confirmed partial response (PR) is defined as a >= 30% decrease from baseline in the sum of longest diameters, confirmed by a second determination of PR at least 4 weeks later. A patient is considered to have measurable disease if they have at least one lesion with a longest diameter of >= 2 cm by conventional CT, or >= 1 cm by spiral CT.


Enrollment: 24
Study Start Date: April 2006
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab + Radiotherapy (no Docetaxel) Biological: cetuximab

Cohorts 1 and 2: 400 mg/m2 (initial dose) 2 hour IV infusion on Day 1, Cycle 1 only.

250 mg/m2, 1 hour IV infusion on Days 8 , 15 and 22 during Cycle 1. 250 mg/m2 (subsequent doses), 1 hour IV infusion on Days 1, 8 , 15 and 22 during subsequent cycles.

Radiation: radiation therapy

Radiation therapy should begin on Day 8 of Cycle 1 and continue through the end of Cycle 2. Refer to Section 12.1 for Radiation Therapy Review.

RT prescription should be PTV (GTV + 2-cm margins on CT scan) to 6,480 cGy in 36 fractions given 5 days a week, 180 cGy per day. The dose is prescribed to the isocenter. The entire treatment should be planned prior to starting treatment to ensure that the plan meets protocol specifications.

Experimental: Cetuximab + Radiotherapy + Docetaxel Biological: cetuximab

Cohorts 1 and 2: 400 mg/m2 (initial dose) 2 hour IV infusion on Day 1, Cycle 1 only.

250 mg/m2, 1 hour IV infusion on Days 8 , 15 and 22 during Cycle 1. 250 mg/m2 (subsequent doses), 1 hour IV infusion on Days 1, 8 , 15 and 22 during subsequent cycles.

Drug: docetaxel

Cohort 2 ONLY: 20 mg/m2 IV over 15 - 30 minutes on Days 8, 15 and 22 of Cycle 1. Concurrent with RT and cetuximab starting at Week 2.

20 mg/m2 IV over 15 - 30 minutes on Days 1, 8, 15 and 22 of Cycle 2.

Radiation: radiation therapy

Radiation therapy should begin on Day 8 of Cycle 1 and continue through the end of Cycle 2. Refer to Section 12.1 for Radiation Therapy Review.

RT prescription should be PTV (GTV + 2-cm margins on CT scan) to 6,480 cGy in 36 fractions given 5 days a week, 180 cGy per day. The dose is prescribed to the isocenter. The entire treatment should be planned prior to starting treatment to ensure that the plan meets protocol specifications.


Detailed Description:

OBJECTIVES:

Primary

  • Test the feasibility and toxicity of combined cetuximab, weekly docetaxel, and concurrent radiotherapy in patients with poor-risk stage III non-small cell lung cancer (NSCLC).

Secondary

  • Evaluate response rates (confirmed and unconfirmed, complete and partial) as well as overall and progression-free survival.
  • Correlate EGFR mutations, KRAS mutations, EGFR/HER2 gene copy number detected by FISH, and protein expression by immunohistochemistry of EGFR-HER signaling pathways, phosphorylation, proliferative markers, apoptotic markers, selected oncogene markers, and markers for angiogenesis in biopsied pre-treatment tumor tissues with response and survival outcomes.
  • Explore possible associations between changes in plasma angiogenic factors (VEGF, IL-8, bFGF) and cytokine levels (IL-6, IL-1α, ICAM, TGF-β, and others) and the risk of treatment-related pneumonitis and esophagitis.

OUTLINE: Patients are enrolled sequentially to 1 of 2 treatment groups.

  • Cohort 1: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, and 22.
  • Cohort 2: Patients receive cetuximab as in group 1 followed by docetaxel IV over 15-30 minutes on days 8, 15, and 22 of course 1 and on days 1, 8, 15, and 22 of course 2.

Initially, 27 patients will be enrolled in Cohort 1. Once all patients in Cohort 1 have discontinued treatment, if toxicity rates are acceptable per protocol specifications, an additional 27 patients will be enrolled to Cohort 2. Treatment in both cohorts repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. All patients also undergo radiotherapy once daily, 5 days a week, beginning on day 8 of course 1 and continuing through course 2 (approximately 7 weeks). Patients with no progressive disease then receive cetuximab alone once weekly. Treatment with cetuximab alone continues in the absence of disease progression for up to 2 years.

After completion of study treatment, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically proven newly diagnosed single, primary, bronchogenic stage IIIA or selected stage IIIB (excluding malignant pleural effusion) non-small cell lung cancer (NSCLC) of one of the following cellular types:

    • Adenocarcinoma
    • Large cell carcinoma
    • Squamous cell carcinoma
    • Unspecified
  • Histology or cytology from involved mediastinal or supraclavicular nodes will be sufficient for diagnosis if a separate primary lesion of the lung parenchyma is clearly evident on radiographs (i.e., a second biopsy will not be required)
  • Underwent positron emission tomography (PET) scan within the past 42 days

    • N2 or N3 mediastinal disease by PET scan OR enlarged nodes on CT scan determined to be N2 or N3 by biopsy
  • Measurable disease, defined as lesions that can be accurately measured in at least one dimension as ≥ 2 cm by conventional techniques or ≥ 1 cm by spiral CT scan

    • Pleural effusion, ascites, bone lesions, and laboratory parameters are not considered measurable disease
  • No brain metastases
  • Malignant pleural effusion allowed provided 1 of the following is true:

    • Present before mediastinoscopy or exploratory thoracotomy AND the pleural fluid is transudate with negative cytology
    • Present only after but not before exploratory or staging thoracotomy AND the pleural fluid is either transudate or exudate with negative cytology
    • Present only on CT scan but not on decubitus chest x-ray AND deemed too small to tap under either CT scan or ultrasound guidance

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1, meeting ≥ 1 of the following criteria OR Zubrod performance status 2 with no co-morbidities or meeting 1 of the following criteria:

    • No co-morbidities
    • FEV_1 < 2 L OR < 1 L with estimated contralateral FEV_1 ≥ 0.6 L
    • DLCO > 10 mL/mm Hg/min
    • Albumin < 0.85 times lower limit of normal
    • Unintentional weight loss > 10% within the past 6 months
    • Controlled congestive heart failure which, in the opinion of the investigator, may become decompensated due to radiotherapy
  • FEV_1 < 2 L OR < 1 L with estimated contralateral FEV_1 ≥ 0.6 L
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Must provide prior smoking history
  • Serum bilirubin normal
  • Meets one of the following criteria:

    • Alkaline phosphatase (AP) ≤ 4 times ULN AND SGOT or SGPT normal
    • AP normal AND SGOT or SGPT ≤ 2.5 times ULN
  • No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I or II cancer from which the patient is currently in complete remission
  • No pregnant or nursing patients
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy or curative surgery for this cancer
  • No prior radiotherapy to the neck and/or thorax for any reason
  • No prior therapy which specifically targets the EGFR pathway
  • No concurrent growth factors (e.g., filgrastim [G-CSF], epoetin alfa, or pegfilgrastim) or amifostine
  • No concurrent intensity-modulated radiotherapy
  • No concurrent prophylactic mediastinal, contralateral hilar, or supraclavicular lymph node radiotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00288054

  Show 77 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Principal Investigator: Yuhchyau Chen, MD, PhD James P. Wilmot Cancer Center
Principal Investigator: Kishan J. Pandya, MD James P. Wilmot Cancer Center
Principal Investigator: Derick H. Lau, MD University of California, Davis
Principal Investigator: Karen Kelly, MD University of Colorado, Denver
Principal Investigator: Laurie E. Gaspar, MD, MBA University of Colorado, Denver
  More Information

No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00288054     History of Changes
Other Study ID Numbers: CDR0000456381, U10CA032102, S0429
Study First Received: February 6, 2006
Results First Received: November 26, 2012
Last Updated: January 2, 2013
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
adenocarcinoma of the lung
large cell lung cancer
squamous cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Docetaxel
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014